A preliminary study on the interaction between Asn-Gly-Arg (NGR)-modified multifunctional nanoparticles and vascular epithelial cells

Liu, Chunxi; Liu, Tingxian; Yu, Xiaoyue; Gu, Yizhu

Aminopeptidase N/CD13 (APN/CD13) is a type II transmembrane protein present in a wide variety of human organs, tissues and cell types (endothelial, epithelial, fibroblast and leukocyte). CD13 has multiple functions related to tumorigenesis, the immune system, and pain 19 . These functions can facilitate the modulation of bioactive peptide responses, such as pain management and vasopressin release. They can also influence body immune functions and major biological events, such as cell proliferation, secretion, invasion and angiogenesis, thereby providing treatment options for various diseases 20 . CD13 can be specifically recognized and bound by the specific sequence of Asn-Gly-Arg (NGR) peptide and exhibits high affinity and specificity toward this moiety 21 . Although CD13 is a ubiquitous enzyme, studies on its expression pattern in normal and neoplastic human tissues suggest that different CD13 forms are expressed in myeloid cells, epithelia and tumor-associated blood vessels 22 . The CD13 isoform which functions as a vascular receptor for the NGR motif was reported to be selectively overexpressed in tumor vasculature and in some tumor cells 21, 23, 24 . In fact, many CD13-targeted therapy based on NGR, such as NGR-drug conjugates 25, 26 , NGR-coated liposomes (http://www.ambrilia.com), NGR-coated PEG-b-PLA polymeric micelles 27 , NGR-modified PEGylated LPD (liposome-polycation-DNA) nanoparticles 28 , CNGRC/PEG/PEI/DNA vector for gene therapy 29 . and so on, are under clinical and late pre-clinical development. Above all, strategy targeting CD13 by NGR for tumor therapy was widely accepted. Characterization of such newly developed formulations is important in the development of vascular-targeted therapies based on the NGR/CD13 system.